A Study of Laquinimod Eye-drops in Healthy Participants

Phase 1

Completed

• Conditions: Eye Diseases
• Interventions: Drug: Placebo; Drug: Laquinimod

• Registration Number: NCT05187403
• Lead Sponsor: Active Biotech AB

Brief Summary

This is a Phase 1 randomized, double-masked, placebo-controlled study performed with healthy participants to assess the safety and tolerability of laquinimod eye-drops.

Detailed Description

Laquinimod administered as an oral capsule formulation has previously been studied in neurodegenerative and autoimmune diseases. The clinical side effect profile of orally administered laquinimod is well-characterized based on this previous experience.

This trial will establish a safe and tolerated dose of laquinimod when administered as an eye-drop formulation following single ascending dose (SAD) and multiple ascending dose (MAD) administrations. There are four planned groups in the SAD-part of the study which will enroll 28 participants, if all dose levels are explored. The subsequent MAD-part of the study will enroll another 28 participants.

Study Timeline

• Study First Submitted: 2021-12-06
• Study Start: 2021-12-09
• Study First Submitted QC: 2022-01-10
• Study First Posted: 2022-01-11
• Status Verified: 2023-01
• Primary Completion: 2023-01-19
• Study Completion: 2023-01-19
• Last Update Submitted: 2023-01-30
• Last Update Posted: 2023-01-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 54

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo - Single Ascending Doses	Placebo	One single dose of placebo eye-drops.
Placebo - Multiple Ascending Doses	Placebo	Eye-drops administered once daily for 14-21 days.
Laquinimod - Multiple Ascending Doses	Laquinimod	Eye-drops administered once daily for 14-21 days. There are up to two planned dose levels. The first dose level will be defined in the SAD-part of the study.
Laquinimod - Single Ascending Doses	Laquinimod	One single dose of laquinimod eye-drops. There are up to four planned dose levels.

Primary Outcome Measures

Name	Time	Method
Adverse events	For 7 days post-dose	Type, frequency, seriousness, severity and relationship to treatment

Secondary Outcome Measures

Name	Time	Method
Investigator-reported eye-toxicities - Corneal fluorescein staining	At screening visit (baseline) and immediately after the intervention	Assessed from change from baseline in corneal fluorescein staining determined using the NEI/Industry Workshop guidelines. The cornea is divided into five sectors (central, superior, inferior, nasal and temporal) and each sector scored on a 4-point scale, where 0= no staining and 3= maximum staining.
Investigator-reported eye-toxicities - Slit lamp examination	Pre-dose (baseline) and immediately after the intervention	Assessed from change from baseline in slit lamp examination parameters (eyelid swelling, eyelid redness, conjunctival redness, conjunctival chemosis, scleral redness, corneal opacity, iris alterations and anterior chamber flare) graded on a 4-point scale where 0= none, 1= mild, 2= moderate, and 3= severe.
Investigator-reported eye-toxicities - Intraocular pressure	At screening visit (baseline) and immediately after the intervention	Assessed from change from baseline in intraocular pressure (mmHg) determined using a Goldmann applanation tonometer.
Investigator-reported eye-toxicities - Funduscopy in mydriasis	At screening visit (baseline) and immediately after the intervention	Assessed from change from baseline in clinical signs detected by indirect funduscopic inspection of the optic disc, macula, retinal vessels and retinal periphery.
Participant-reported eye-toxicities	Pre-dose (baseline) and immediately after the intervention	Assessed from change from baseline in ocular symptoms score determined using a Visual Analogue Scale with 0-100 range, where 0= no symptom and 100= worst possible discomfort.
Investigator-reported eye-toxicities - BCVA	Pre-dose (baseline) and immediately after the intervention	Assessed from change from baseline in Best Corrected Visual Acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study research group (ETDRS) visual acuity chart with objective and subjective refraction.
Trough plasma concentration of laquinimod at steady-state	On the last three days of multiple dosing	Minimal plasma concentration (Cmin,ss) of laquinimod as assessed from samples collected pre-dose on Days 12, 13 and 14 within the multiple-dose arm
Peak plasma concentration of laquinimod	Over up to 21 days after (last) dose	Maximal plasma concentration (Cmax) of laquinimod as assessed from samples collected pre-dose and at frequent intervals over 7 days after (last) dose
Time to peak plasma concentration of laquinimod	Over up to 21 days) after (last) dose	Time to maximal plasma concentration (tmax) of laquinimod as assessed from samples collected pre-dose and at frequent intervals over 7 days after (last) dose
Systemic exposure of laquinimod	Over up to 21 days after (last) dose	Area under the plasma concentration time curve (AUC) of laquinimod

Trial Locations

Locations (1)

Clinical trial center at Medical University Vienna; 🇦🇹 Vienna, Austria